The proposed K22 is intended to provide initial support allowing Dr. Robert McKallip to gain experience and knowledge necessary to foster his transition to an independent investigator. Dr. Robert McKallip was recently appointed to a faculty position in the Department of Microbiology and Immunology at the Virginia Commonwealth University and he is a member scientist of the Massey Cancer Center. Dr. McKallip's association with the Dept. of Microbiology and Immunology and Massey Cancer Center provides him access to a wide range of investigators and modern equipment creating an environment highly supportive for developing a career in cancer research. He plans to use this award to further strengthen some critical skills and become proficient in new techniques, such as confocal microscopy, and siRNA gene silencing. Importantly, Dr. McKallip plans to use the newly acquired skills and the preliminary results from the proposed study to apply for independent funding from competitive research grant programs from the NIH/NCI, or an R01 equivalent research grant program. His long-term goals are to extend his postdoctoral work examining the role of CD44 in lymphocyte-mediated damage to endothelial cells to independent work examining the possible role of CD44 isoforms in the recognition and interactions of activated lymphocytes with melanoma. In initial work, he demonstrated that following exposure to IL-2, there is a significant increase in the expression of CD44 and that lymphocytes expressing high levels of CD44 have potent cytolytic activity. However, little is known about the role of CD44 expressed by activated lymphocytes in the interactions with melanoma. Therefore, he proposes to examine the role of CD44 in the interaction between IL-2-activated lymphocytes and melanoma and to test the hypothesis that lymphocytes expressing high levels of CD44 (CD44hi) are responsible for mediating lysis of melanoma tumor cells and that this increase in CD44 expression is directly due to increased expression of specific CD44 isoforms. Furthermore, he proposes to examine the potential use of the CD44hi cells in the treatment of melanoma. [unreadable] [unreadable]